Our research is directed towards understanding the regulation of gene expression in higher organisms. We are currently focusing on the mouse metallothionein genes. The products of these genes are small proteins that bind heavy metals such as cadmium, zinc and copper. These genes are regulated at the transcriptional level by both glucocorticoid hormones and heavy metals. We are using recombinant DNA techniques and cell transformation to define the region of the metallothionein genes that are essential for regulation of expression. The long range goal is to reproduce the regulation in a defined cell-free system. We are also studying the role of metallothioneins in zinc metabolism and prevention of heavy metal toxicity. These studies are being pursued in cadmium sensitive and resistant cell lines as well as inbred mouse strains.